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PLoS One. 2016 Mar 30;11(3):e0150271. doi: 10.1371/journal.pone.0150271. eCollection 2016.

Establishment and Biological Characterization of a Panel of Glioblastoma Multiforme (GBM) and GBM Variant Oncosphere Cell Lines.

Author information

1
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
2
Johns Hopkins Physical Science Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States of America.
3
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
4
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
5
Department of Neurosurgery, Aurora Neuroscience Innovation Institute, Milwaukee, WI, United States of America.

Abstract

OBJECTIVE:

Human tumor cell lines form the basis of the majority of present day laboratory cancer research. These models are vital to studying the molecular biology of tumors and preclinical testing of new therapies. When compared to traditional adherent cell lines, suspension cell lines recapitulate the genetic profiles and histologic features of glioblastoma multiforme (GBM) with higher fidelity. Using a modified neural stem cell culture technique, here we report the characterization of GBM cell lines including GBM variants.

METHODS:

Tumor tissue samples were obtained intra-operatively and cultured in neural stem cell conditions containing growth factors. Tumor lines were characterized in vitro using differentiation assays followed by immunostaining for lineage-specific markers. In vivo tumor formation was assayed by orthotopic injection in nude mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA profiling.

RESULTS:

Thirteen oncosphere lines derived from GBM and GBM variants, including a GBM with PNET features and a GBM with oligodendroglioma component, were established. All unique lines showed distinct genetic profiles by STR profiling. The lines assayed demonstrated a range of in vitro growth rates. Multipotency was confirmed using in vitro differentiation. Tumor formation demonstrated histologic features consistent with high grade gliomas, including invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts derived from the GBM variants maintained histopathological features of the primary tumors.

CONCLUSIONS:

We have generated and characterized GBM suspension lines derived from patients with GBMs and GBM variants. These oncosphere cell lines will expand the resources available for preclinical study.

PMID:
27028405
PMCID:
PMC4814135
DOI:
10.1371/journal.pone.0150271
[Indexed for MEDLINE]
Free PMC Article

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